We have discovered that human sperm can rapidly bind and penetrate human lymphocytes in vitro. These interactions are selective for cells bearing surface HLA class II molecules, and data for antibody inhibition studies suggest that the lymphocyte surface receptor for sperm is the HLA-DR molecule, while the corresponding sperm recognition ligand may be a structure similar to T cell surface T4. Two goals are set for the upocoming project period. These are: (1) to identify the sperm surface T4- crossreactive ligand and to define its role in recognition of lymphocyte surface HLA-DR, and (2) to test for a role for sperm- lymphocyte interactions in the sexual transmission of AIDS. Sperm-blood cell interactions in humans may reflect the presence on blood cells of molecules similar to the sperm receptors on the egg envelopes. Definition of a role for the MHC glycoproteins and the Ig-related T4 molecule in human sperm-lymphocyte interactions, therefore, provides the first evidence for a relationship between gametic and somatic self-recognition systems in higher chordates. These studies grew out of our work with marine protochordates, which has been directed toward studies of the early evolution of the related major histocompatibility complex (MHC) and immunoglobulin (Ig) multigene families. In the colonial tunicate Botryllus, we have defined an MHC-like histocompatibility gene system that controls both graft rejection and fertilization between colonies. This condition may be common to all tunicates; interactions between co-cultured sperm and blood cells of the solitary tunicate Ciona, like the intercolony graft rejections in Botryllus, follow the established genetics of mating type. The occurrence of specific sperm-lymphocyte interactions in humans, and the apparent involvement of MHC class II structures and the Ig-related T4 molecule in these events, thus adds to the evidence for homology between the protochordate and vertebrate major hisotcompatibility genes.